Matrix Metalloproteinases and Hypertension

The matrix metalloproteinases (MMPs) are known for quite some time to play essential roles in this remodeling process of arteries found in hypertension, as will be discussed here. More recently, evidence indicates that some of them may not only influence hypertension due to their effect in remodeling but possibly by direct mechanisms such as the proteolytic change of vasoactive mediators. The most studied MMP in animal models of hypertension is MMP-2, and many such studies are described here. After a brief description of MMPs, we discuss data on MMPs in hypertension in three sections: findings on arteries, findings on the heart, and on the final section we then briefly discuss some other issues that may indicate that MMPs are related to hypertension in other yet unexplored ways. In this review we also highlight data showing the protective effects of MMP inhibition in arteries, heart, and kidney. MMP inhibition appears to be a relevant target for newer pharmacological intervention in hypertension. Doxycycline is the MMP inhibitor most widely used in cell cultures, animal studies on hypertension, and is a drug approved for commercial use for periodontal disease in the United States. The refinement of MMP assays and the specific delivery of different MMPs may highlight the specific role of each MMP in the different types of hypertension, enabling the use of a rational approach for a more specific inhibition of them in hypertension, so that target organs are more protected.